Biol. Pharm. Bull. 28(4) 574—579 (2005)

cent studies have shown that green tea and its component polyphenol have a chemopreventing effect on models of cancer in vitro and in vivo. ( )-Epigallocatechin-3-gallate (EGCG) is a major component of polyphenols in green tea and is reported to inhibit the proliferation and to induce apoptosis in cancer cells. A typical cup of green tea contains 100—150 mg of catechins, including 8% ( )-epicatechin (EC), 15% ( )-epigallocatechin (EGC), 15% ( )-epicatechin-3-gallate (ECG), and 50% EGCG. Among these catechins, EGCG is the most potent component for inhibition of the growth of cancer cells and induction of apoptosis. The molecular mechanism of the chemopreventing effect of green tea can be accounted for by the fact that green tea catechins including EGCG have an inhibitory effect on the growth of cancer cells; however, the precise mechanism of growth inhibition of catechins remains to be elucidated. Apoptosis is a programmed cell death induced by extracellular stimuli or internal signaling pathways during such processes as embryogenesis and organ development. Signaling pathways for apoptosis induced by extracellular stimuli include two major cascades; one triggered by the binding of a signaling factor such as FAS ligand to the cognate death receptor and including the activation of caspase-8 followed by caspase-3, the other initiated by stress or toxic stimuli whereby the induced signal for apoptosis is transduced through activation of JNK/p38 and a mitochondrial pathway which includes activation of caspase-9 followed by caspase3. A recent study reported that oxidative stress induced by EGCG is a major effector inducing apoptosis through the JNK/p38 pathway, whereas, Hayakawa et al. reported that EGCG binds to specific receptor proteins including FAS and induces apoptosis in leukemia U937 cells. In this study, we examined the effect of green tea catechins on a variety of cell lines established from gastric carcinoma, focusing on the chemopreventing effect of green tea as a functional food. Four cell lines established from gastric carcinoma cells in various states were treated with tea catechins and the inhibition of cell growth and induction of apoptosis were examined. The results suggested that the cell lines differed in their susceptibility to EGCG treatment: MKN-45, established from a poorly differentiated tubular adenocarcinoma, was the most sensitive to the EGCG treatment. To evaluate the chemopreventing effect of green tea as a beverage, the synergistic effect of catechins included in the tea was examined. EC had almost no effect on the cell growth or induction of apoptosis. However, a significant synergistic effect on the induction of apoptosis was observed when EC was combined with other catechins. Furthermore, we found that catalase specifically canceled the synergistic effect of EC and EGCG, suggesting that the synergism involved production of reactive oxidative species, such as hydrogen peroxide.